External Validation of Joint Propagation Model‐Based Tau PET CenTauR units

Abstract Background The Joint Propagation Model (JPM)‐based CenTauR scale was recently introduced to harmonize tau‐PET quantification across different radiotracers. This study examined how CenTauR harmonization enhances the comparability of tau‐PET quantification across matched cohorts using different tracers. The evaluation focused on three key aspects: (1) comparing tau‐PET positivity rates as defined by CenTauR, (2) evaluating its diagnostic accuracy for symptomatic AD, and (3) analyzing longitudinal changes in tau‐PET rates over time. Method The JPM, developed by the CPAD‐led Tau PET Harmonization Working Group (Leuzy et al., Alzheimers Dement. 2024; Figure 1A), models relationships between anchor point subjects and head‐to‐head tau‐PET SUVR data onto the CenTauR scale, providing conversion equations for multiple tracers. JPM equations were applied to [ 18 F]flortaucipir SUVR (Meta‐temporal ROI) data from 561 cognitively impaired participants in the ADNI and OASIS‐3 studies. Using ROC analysis, we determined the CenTauR cut‐off for positivity (T+) that maximized the Youden index for discriminating between FDA‐approved positive/negative visual reads. Three separate cohorts, scanned using [ 18 F]flortaucipir (ADNI), [ 18 F]MK‐6240 (CPAS), and [ 18 F]RO‐948 (BioFINDER‐2), were matched 1:1 by age, MMSE, amyloid‐β, and clinical diagnosis. CenTauR‐based metrics were compared across these cohorts. Result A cut‐off of 18 CenTauRs was found to optimally classify [ 18 F]flortaucipir PET visual reads (Figure 1B). The matching procedure identified 1089 participants (363 per cohort). The frequency of T+ using the 18 CenTauRs cut‐off for the Meta‐Temporal ROI was highly comparable across tracers across groups, except for the Aβ‐positive cognitively unimpaired group, where variability was more pronounced due to a smaller sample size (Figure 2A). Similarly, tau‐PET discriminative accuracy for symptomatic AD vs controls remained similar across [ 18 F]flortaucipir and [ 18 F]MK‐6240 (Figure 2B). In a separate sample of 212 matched participants from ADNI ([ 18 F]flortaucipir) and AIBL ([ 18 F]MK‐6240) with baseline and 1‐year follow‐up tau‐PET scans, 1‐year change in CenTauRs was comparable (Figure 2C). An exploratory voxelwise transformation, utilizing the Meta‐Temporal conversion equation in a representative case scanned with both [ 18 F]flortaucipir and [ 18 F]MK‐6240, demonstrates the potential for voxelwise CenTauR harmonization (Figure 3). Conclusion These analyses suggest that CenTauR harmonization increases the comparability of tau‐PET data acquired with different tracers. Additional validation analyses with larger cohorts including other radiotracers ([ 18 F]PI‐2620) are underway.

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Journal
Alzheimer s & Dementia
Published
2025-12-01
DOI
https://doi.org/10.1002/alz70856_106362
Primary Topic
Dementia and Cognitive Impairment Research
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article
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article

External Validation of Joint Propagation Model‐Based Tau PET CenTauR units

Vincent Doré, Tobey J. Betthauser, Christopher C. Rowe, Rik Ossenkoppele et al.
Alzheimer s & Dementia
Dementia and Cognitive Impairment Research
article

External Validation of Joint Propagation Model‐Based Tau PET CenTauR units

Vincent Doré, Tobey J. Betthauser, Christopher C. Rowe, Rik Ossenkoppele, Eric D. Hostetler, Santiago Bullich, Sulantha Mathotaarachchi, Leonardo Iaccarino, Johannes Gnörich, Samantha Budd Haeberlein, Nadine Tatton, Michael J. Pontecorvo, Suzanne L. Baker, Roger N. Gunn, Brian J. Lopresti, Hartmuth C. Kolb, Diane T. Stephenson, Yashmin Karten, Mark A. Mintun, A. Charil, Olivia Lutz, Alex Whittington, Oskar H. Hansson, Gregory Klein, Marta Marquié, Ziad S. Saad, M. Carrillo, Billy Dunn, Xiaxie Mao, Sandra Sanabria, Antoine Leuzy, Alexis Moscoso, Philip S. Insel, Matthias Brendel, Konstantinos Chiotis, William J. Jagust, Andrew W. Stephens, Qi Huang, Christopher G Schwarz, Gil D. Rabinovici, Mercè Boada, Fang Xie, Emily Olafson, Keith A. Johnson, Pedro Rosa‐Neto, Matteo Tonietto, Ronald Petersen, Emily C. Collins, Michael C. Irizarry, Ruben Smith, Lars Lau Raket, Makoto Higuchi, Ioannis Pappas, Sterling C. Johnson, R. Matthew Hutchison, Clifford R. Jack, Victor L. Villemagne, Jessica Collins
article en

Abstract

Abstract Background The Joint Propagation Model (JPM)‐based CenTauR scale was recently introduced to harmonize tau‐PET quantification across different radiotracers. This study examined how CenTauR harmonization enhances the comparability of tau‐PET quantification across matched cohorts using different tracers. The evaluation focused on three key aspects: (1) comparing tau‐PET positivity rates as defined by CenTauR, (2) evaluating its diagnostic accuracy for symptomatic AD, and (3) analyzing longitudinal changes in tau‐PET rates over time. Method The JPM, developed by the CPAD‐led Tau PET Harmonization Working Group (Leuzy et al., Alzheimers Dement. 2024; Figure 1A), models relationships between anchor point subjects and head‐to‐head tau‐PET SUVR data onto the CenTauR scale, providing conversion equations for multiple tracers. JPM equations were applied to [ 18 F]flortaucipir SUVR (Meta‐temporal ROI) data from 561 cognitively impaired participants in the ADNI and OASIS‐3 studies. Using ROC analysis, we determined the CenTauR cut‐off for positivity (T+) that maximized the Youden index for discriminating between FDA‐approved positive/negative visual reads. Three separate cohorts, scanned using [ 18 F]flortaucipir (ADNI), [ 18 F]MK‐6240 (CPAS), and [ 18 F]RO‐948 (BioFINDER‐2), were matched 1:1 by age, MMSE, amyloid‐β, and clinical diagnosis. CenTauR‐based metrics were compared across these cohorts. Result A cut‐off of 18 CenTauRs was found to optimally classify [ 18 F]flortaucipir PET visual reads (Figure 1B). The matching procedure identified 1089 participants (363 per cohort). The frequency of T+ using the 18 CenTauRs cut‐off for the Meta‐Temporal ROI was highly comparable across tracers across groups, except for the Aβ‐positive cognitively unimpaired group, where variability was more pronounced due to a smaller sample size (Figure 2A). Similarly, tau‐PET discriminative accuracy for symptomatic AD vs controls remained similar across [ 18 F]flortaucipir and [ 18 F]MK‐6240 (Figure 2B). In a separate sample of 212 matched participants from ADNI ([ 18 F]flortaucipir) and AIBL ([ 18 F]MK‐6240) with baseline and 1‐year follow‐up tau‐PET scans, 1‐year change in CenTauRs was comparable (Figure 2C). An exploratory voxelwise transformation, utilizing the Meta‐Temporal conversion equation in a representative case scanned with both [ 18 F]flortaucipir and [ 18 F]MK‐6240, demonstrates the potential for voxelwise CenTauR harmonization (Figure 3). Conclusion These analyses suggest that CenTauR harmonization increases the comparability of tau‐PET data acquired with different tracers. Additional validation analyses with larger cohorts including other radiotracers ([ 18 F]PI‐2620) are underway.

Alzheimer s & DementiaVol. 21(S2)
University of Southern California (US), Roche (Switzerland) (CH), Alzheimer's Association (US), Brigham and Women's Hospital (US), Montreal Neurological Institute and Hospital (CA), Biogen (United States) (US), Johnson & Johnson (United States) (US), University of Wisconsin–Madison (US), Harvard University (US), Lawrence Berkeley National Laboratory (US), Eli Lilly (United States) (US), University of Pittsburgh (US), University of California, San Francisco (US), Lund University (SE), United States Military Academy (US), Critical Path Institute (US), Breast Cancer Network Australia (AU), LMU Klinikum (DE), Universitat Internacional de Catalunya (ES), University of Illinois Chicago (US), University of Chicago (US), Invicro (United Kingdom) (GB), Enigma Diagnostics (United Kingdom) (GB), University Memory and Aging Center (US), Alzheimer’s Disease Neuroimaging Initiative (US), National Institutes for Quantum Science and Technology (JP), Fundació ACE (ES), Mayo Clinic in Arizona (US), Mitsubishi Corporation (United Kingdom) (GB), Skåne University Hospital (SE), Australian e-Health Research Centre (AU), Wisconsin Division of Public Health (US), Instituto de Investigación Sanitaria de Santiago (ES), Eisai (United States) (US), Amsterdam University Medical Centers (NL), Huashan Hospital (CN), McGill University (CA), Ludwig-Maximilians-Universität München (DE), University of California, Berkeley (US)
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Dementia and Cognitive Impairment Research
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